Bio-products are products produced by conventional technologies or modern biotechnologies from microorganisms, cells, animal or human tissues and body fluids, etc., as raw materials for prophylaxis, therapy and diagnosis of human diseases. Blood products, belonging to bio-products, mainly refer to bioactive preparations prepared by biological processes or by separation and purification technologies from healthy human blood as raw material, including human serum albumin, albumin prepared from human placenta, human immunoglobulin for intravenous injection, human immunoglobulin for intramuscular injection, histamine human immunoglobulin, specific immunoglobulin, hepatitis B, hydrophobia, tetanus immunoglobulin, human coagulation factor VIII, human prothrombin complex concentrate, human fibrinogen, anti-lymphocyte immunoglobulin, etc. The blood products, for purposes of treatment and passive immunization, play an irreplaceable role in providing emergency medical services, rescuing the wounded in wars, and preventing and treating some specific diseases.
As the blood products are prepared from human plasma, usually by mixing a plurality of portions of plasma and then processing by a certain separation and purification technology, theoretically, blood-borne diseases may be spread through the blood products. At present, the common viruses carried and spread by blood preparations mainly include HBV, HCV, HIV and HTLV-1, CMV, EBV, HAV, parvoviruses, etc.
To improve the safety of the blood products, according to requirements of the relevant guidance and principle, the production process of blood products must have the ability to remove/inactivate some viruses, and there should be specific virus removal/inactivation approaches available during the production. The virus inactivation approaches for the blood products are classified into physical inactivation and chemical inactivation. The physical inactivation typically includes pasteurization, dry-heating, γ-ray irradiation and short-wave ultraviolet irradiation. The chemical inactivation typically includes organic solvent/decontaminant (S/D) treatment, low pH incubation, caprylate inactivation and photochemical treatment. The chemical inactivation has good effect on lipid enveloped viruses only but very little on non-lipid enveloped viruses; furthermore, one or more biochemical reagents need to be added in the chemical inactivation, resulting in uncertain long-term safety. (Song Qingshuang, et al., Progress of Virus Inactivation and Removal Process for Blood Products, Letters in Biotechnology, 2012, No. 04). The majority of bio-products are manufactured into end products by vacuum freeze-drying. Dry-heating inactivation is a feasible way of terminal inactivation.
An existing terminal dry-heating inactivation method, where a vacuum freeze-drying product is inactivated by dry-heating under vacuum conditions, has good inactivation effect on lipid enveloped viruses such as HBV but poor inactivation effect on highly heat resistant lipid enveloped viruses, particularly on parvoviruses. For example, the researches of Roberts, et al. indicated that different non-lipid enveloped viruses had different heat resistance under the same treatment conditions: only 2.2 log of PPVs may be inactivated when treated by dry-heating at 80° C. even for 72 h. The report of Kim, et al, indicated that, the titer of PPVs (Porcine Parvoviuses) was merely reduced by 1.90 log by treating FVIII concentrate in a water bath at 100° C. for 30 min. Xiang Qingqun, et al., Effects of Final Dry-heating on Non-enveloped Viruses in Coagulation Factor Concentrate, Foreign Medical Sciences, Section of Bilogics for Prophylaxis, Diagnosis and Therapy, 1995, No. 06, pointed out that, after added into SD-inactivated high-purity FVIII and then freeze-dried, CPVs (Human Parvoviuses) were vacuum dry-heated upon the residual moisture of less than 2%, and only 2.1 log of CPVs was inactivated when treated at 80° C. for 72 hrs or at 90° C. for 10 hrs.